Periodontal disease is an inflammatory disorder of the supporting tissue of the teeth. In the absence of control, the chronic inflammatory process will destroy the hard and soft tissues which support the teeth and eventually result in the loss of those teeth.
At present, the treatment of periodontal diseases is one of the most difficult problems in dentistry and periodontal disease is the major cause of tooth loss in adults. Since the introduction of water fluoridation, as well as the widespread use of fluoride containing dentifrices by children in the United States, tooth loss due to tooth decay among children and adolescents has dramatically decreased. Unfortunately, the opportunity to become afflicted with periodontal disease has concomitantly increased.
The two most common periodontal diseases are chronic gingivitis which is inflammation of the gingiva, and chronic destructive periodontitis, which results from progressive resorption of the alveolar bone, increasing the mobility of the teeth and, in an advanced stage, tooth loss.
The prevention and treatment of periodontal disease has in the past primarily involved maintaining good oral hygiene, eliminating sub-gingival calcului, protruding fillings and soft tissue, as well as intraosseous pockets and occlusal traumas and establishing a periodontal environment which is easily kept clean by the patient. This treatment is, unfortunately, not only protracted and expensive but also tends to require repetition throughout the individual's lifetime. It is frequently necessary to repeat periodontal surgery and even so, the long term effectiveness of the surgery has been limited.
Belgium Patent No. 900481 relates to a method of preventing or treating periodontal disease by using as the active agent either ibuprofen or flurbiprofen or a pharmaceutically acceptable lower alkyl salt or ester of these compounds administered orally, topically or buccally.
Thiele, in U.S. Pat. Nos. 4,097,604, 4,214,006 and 4,215,144 discloses a composition for the treatment of gingivitis and related periodontal diseases of the gingival tissue in which one of the components is a non-necrotic fatty acid compound which is prepared from an unsubstituted, unsaturated fatty acid having at least one double bond. These compounds are thought to be salts or esters and examples of the fatty acids used have 1, 2 or 3 double bonds. Included within the fatty acids set forth is 15-octadecenoic acid (trans form) CH.sub.3 CH.sub.2 CH=CH(CH.sub.2).sub.13 COOH.
Plaque has been determined to be the major etiologic factor in periodontal disease. It has been found that the inflammatory response induced by the plaque is responsible for most of the destruction associated with the disease.
Considerable evidence has implicated prostaglandin, particularly prostaglandin-E.sub.2 (PGE.sub.2), as components of the inflammatory reaction. Goodson et al., Prostaglandins, 6, 81-85 (1984) and El Attar et al., J. Periodontol, 52, 16-19 (1981) demonstrated that PGE.sub.2 levels are elevated in inflamed gingiva when compared to normal gingiva. Offenbacher et al., J. Periodont. Res., 21, 101-112 (1986) demonstrated that extremely high levels of PGE.sub.2 are present at periodontal sites of active attachment loss and low at sites which are in remission, i.e. there is no longitudinal attachment loss. The PGE.sub.2 level in diseased tissue approximates 1 uM (Offenbacher et al. J. Periodon. Res. 19, 1-13 (1984)) which is a pharmacologically active concentration when tested in various model systems to induce vasodilation, bone resorption and other pro-inflammatory responses. Despite this evidence for the key role of PGE.sub.2 in the pathogenesis of periodontal disease, relatively few studies have examined the use of drugs which inhibit PGE.sub.2 synthesis in an attempt to retard or prevent periodontal tissue destruction.
It is the object of this invention to provide a new method and composition for the control and treatment of periodontal diseases. This and other object of the invention will become apparent to those of ordinary skill in this art from the following detailed description.